title: Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, induces the production of anti-inflammatory cyclodepsipeptides from Beauveria felina.
abstract: The addition of the histone deacetylase inhibitor suberoylanilide hydroxamic acid to a culture of the filamentous fungus Beauveria felina significantly changed its secondary metabolite profile and led to the isolation of eight compounds, including three new cyclodepsipeptides, desmethylisaridin E (1), desmethylisaridin C2 (2), and isaridin F (3), along with five known cyclodepsipeptide compounds. Isaridin F (3) possesses a cyclodepsipeptide ring with N-methylbutyric acid, which is rare in natural peptides. Absolute configurations of the new cyclodepsipeptides were achieved by Marfey's method. The anti-inflammatory activity of the isolated compounds was investigated through evaluating their effect on superoxide anion production and elastase release by FMLP-induced human neutrophils. Among the tested compounds, desmethylisaridin E (1) inhibited superoxide anion production and desmethylisaridin C2 (2) inhibited elastase release, with IC50 values of 10.00 ± 0.80 and 10.01 ± 0.46 μM, respectively.
authors.affiliation: Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan, Republic of China.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Chung
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Shazly
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Chuang
authors.forename: Tsong-Long
authors.initials: TL
authors.lastname: Hwang
authors.forename: Teigo
authors.initials: T
authors.lastname: Asai
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Oshima
authors.forename: Mohamed L
authors.initials: ML
authors.lastname: Ashour
authors.forename: Yang-Chang
authors.initials: YC
authors.lastname: Wu
authors.forename: Fang-Rong
authors.initials: FR
authors.lastname: Chang
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D052982:Beauveria / Q000737:chemistry*; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009504:Neutrophils / Q000187:drug effects; D019906:Nuclear Magnetic Resonance, Biomolecular; D013481:Superoxides / Q000378:metabolism; D000077337:Vorinostat
chemical_list: D000893:Anti-Inflammatory Agents; D047630:Depsipeptides; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C584045:desmethylisaridin C2; C584044:desmethylisaridin E; C584046:isaridin F; D013481:Superoxides; D000077337:Vorinostat